tbuckley/cabot-search huggingface dataset:
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study).
Authors: Sherise C. Rogers, Ilyas Sahin, Jesus C. Fabregas, Ibrahim Nassour, Brian Hemendra Ramnaraign, Kathryn Hitchcock, Steven J. Hughes, Ji-Hyun Lee, Omar Roger Kayaleh, Anita Ahmed Turk, Z. Hugh Fan, Karen Bullock Russell, David L. DeRemer, Thomas J. George
Journal: Journal of Clinical Oncology (2023)

TPS778 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multidisciplinary GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NEO-N-IRI regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day postoperative complication rate. Microbiota specimens will be collected for exploratory analysis. Clinical trial information: NCT03483038 . [Table: see text]
Intra-arterial gemcitabine vs IV gemcitabine PK substudy in patients with locally advanced pancreatic cancer.
Authors: Amer H. Zureikat, Michael J. Pishvaian, Kenneth Meredith, Hassan Hatoum, Emmanuel E. Zervos, Reza Nazemzadeh, Paula M. Novelli, Alex Tsobanoudis, Ramtin Agah
Journal: Journal of Clinical Oncology (2023)

728 Background: Localized dual-balloon-mediated, intra-arterial delivery of Gemcitabine (IAG) directly into tumors/tissue can lead to higher local drug potency 1 . Furthermore, IAG may lead to decreased systemic drug concentration and associated side effects. In patients with Locally Advanced Pancreatic Cancer (LAPC), this approach is currently being tested in a contemporary Phase III clinical trial, TIGeR-PaC. Herein we report the results of a 10-patient PK analysis sub-study within TIGeR-PaC. Methods: We analyzed a total of 10 subjects from 5 sites who received intra-arterial gemcitabine with the RenovoCath dual balloon catheter at 1000mg/m 2 over 20 minutes. The target treatment artery was either the celiac axis (n=5) or the superior mesenteric artery (n=5). Samples were drawn at T = -5, 10, 15, 20, 30, 40, 60, and 90 minutes from the onset of infusion. At each timepoint, we collected 2mL of blood in heparinized tubing containing 25 mcg/mL of tetrahydrouridine. The blood samples were then centrifuged collect, freeze, and ship the plasma to a reference lab to perform a gemcitabine assay. The PK parameters for a single dose was estimated for C max , AUC, clearance, and distribution volume based on the terminal phase. These values are compared to historical data for intravenous gemcitabine (IVG) infusion at 1000mg/m 2 over 30 minutes 2 . Results: At this time, data has been analyzed for 4 of 8 collected samples. We expect to complete collection and analysis of all 10 samples by November of 2022. We show results available so far; historical values for IVG are given as a reference point. The results suggest that IAG is associated with decreased systemic exposure of gemcitabine compared to IVG. Conclusions: Localized dual-balloon-mediated, intra-arterial delivery of gemcitabine can lead to decreased systemic levels of gemcitabine. This approach increased local potency and may be beneficial in decreasing gemcitabine-related systemic side effects. 1. Farsad K, et al. 04:21 PM Abstract No. 392 . J Vasc Intervent Radiol 2019;30(3):S172. doi:10.1016/j.jvir.2018.12.467. 2. Chow ECY, Zirkelbach JF. Clinical Pharmacology and Biopharmaceutics Review(s) {209604Orig1s000}. FDA: Center for Drug Evaluation and Research. Clinical trial information: NCT03257033 . [Table: see text]
A phase I dose escalation study of carbon-ion radiotherapy for pancreatic cancer.
Authors: Makoto Shinoto, Hirotoshi Takiyama, Tetusro Isozaki, Shigeru Yamada
Journal: Journal of Clinical Oncology (2023)

TPS768 Background: Despite recent advances in chemotherapy and radiotherapy, the prognosis of unresectable locally pancreatic cancer (LAPC) patients remains poor. To improve the outcome, we have developed carbon ion radiotherapy (C-ion RT) for pancreatic cancer and have shown good results against conventional photon therapy. Compared to conventional photon therapy, C-ion RT can safely administer higher doses, and we find the possibility of long-term survival for some unresectable LAPC. Currently, C-ion RT is performed using 55.2 Gy (RBE) in 12 fractions. However local control is not satisfactory. Further dose escalation needs to be safely administered to further improve outcomes. We have developed a new treatment strategy: intensity-modulated ion therapy using the simultaneous integrated boost method and the linear transfer energy (LET) optimization method. We believe that these cutting-edge technologies will allow for a more intensive effect on pancreatic cancer. Thus, we started a clinical trial to evaluate the safety of dose escalation using these novel techniques. Methods: Eligibility included pathological or clinical confirmation of pancreatic cancer without distant metastasis. Carbon ion radiotherapy is given in 12 fractions over 3 weeks. The radiation doses are set in four steps, with increases ranging from 55.2 Gy (RBE) to 67.2 Gy (RBE). A minimum of three patients is enrolled in each cohort, and if there is no dose limiting toxicity (DLT), a dose escalation is performed. The primary endpoint is acute adverse events; the secondary outcomes are late adverse events, local control rate, and overall survival. We started this trial in September 2021. Cohort 1 has been completed without DLT. Cohort 2 is now starting enrollment. Clinical trial information: jRCTs032210292 .
Trifluridine/tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer: The phase 3 randomized SUNLIGHT study.
Authors: Josep Tabernero, Gerald W. Prager, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe Melo Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna Papai, Pierre-guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik Paul Modest, Karim A. Benhadji, Ronan Fougeray, Catherine Leger, Nadia Amellal, Julien Taieb
Journal: Journal of Clinical Oncology (2023)

4 Background: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (Bev) demonstrated promising efficacy in a randomized phase 2 trial of heavily pretreated patients (pts) with metastatic colorectal cancer (mCRC). SUNLIGHT was conducted to confirm these findings. Methods: The global phase 3 SUNLIGHT study enrolled pts aged ≥18 years with histologically confirmed mCRC, ECOG PS 0/1, and treated with 1-2 prior chemotherapy regimens in an advanced setting, including fluoropyrimidines, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody (if medically considered) and/or anti-EGFR monoclonal antibody for RAS wild-type tumors. Pts were randomised (1:1) to receive FTD/TPI (35 mg/m 2 twice daily on days 1–5 and 8–12 of each 28-day cycle) alone or combined with Bev (5 mg/kg on days 1 and 15). Primary endpoint was overall survival (OS). Results: Between Nov 2020 and Feb 2022, 492 pts were randomised to receive FTD/TPI + Bev (n = 246) or FTD/TPI (n = 246). Baseline characteristics were balanced between arms. FTD/TPI + Bev significantly extended OS over FTD/TPI, median OS was 10.8 months vs 7.5 months, respectively (HR, 0.61; 95% CI, 0.49, 0.77; P&lt; 0.001). OS rates at 12 months were 43% in the FTD/TPI + Bev arm and 30% in the FTD/TPI arm. Median progression-free survival was 5.6 months in the FTD/TPI + Bev arm and 2.4 months in the FTD/TPI arm (HR, 0.44; 95% CI, 0.36,0.54; P&lt; 0.001). Grade ≥3 adverse events (AEs) were not significantly increased in the FTD/TPI + Bev arm vs the FDT/TPI arm (72.4% vs 69.5%). No new safety signals were noted. Conclusions: FTD/TPI + Bev provided a statistically significant and a clinically meaningful 3.3-month improvement in OS, extending mOS up to 10.8 months, with a 39% reduction in the HR of death in pts with refractory mCRC and with a predictable and acceptable safety profile. Clinical trial information: NCT04737187 .
Clinical outcomes of endoscopic resection for gastrointestinal stromal tumor originating from the muscularis propria: A single-center experience.
Authors: Moonwon Lee, Gwang Ha Kim, Bong Eun Lee, Dong Chan Joo
Journal: Journal of Clinical Oncology (2023)

407 Background: With the remarkable advance of endoscopic techniques, endoscopic submucosal dissection (ESD) has become an effective and safe treatment modality for various gastrointestinal tumors (GISTs). However, there is still a lack of evidence on endoscopic treatment of GISTs in the stomach. We aimed to investigate the efficacy and safety of ESD for gastric GISTs and to assess possible predictive factors for incomplete resection. Methods: Between October 2008 and July 2022, a total of 35 patients with gastric GIST underwent ESD at our hospital. Clinicopathologic characteristics of patients and GISTs, therapeutic outcomes, adverse events and follow-up outcomes were evaluated. Results: The overall rates of en bloc resection and complete resection were 77.1% (27/35), 68.6% (24/35), respectively. The median procedure time was 47.3 minutes (range, 15–131 minutes). The procedure-related bleeding and perforation rates were 2.9 % and 17.1%, respectively. In univariate analyses, EUS growth pattern (intraluminal growth, p = 0.027) was independently associated with complete resection. During the median follow-up period of 15.4 months (range, 5.7 – 129 months) in 35 patients except two patients who underwent surgery and one patient who failed to follow up, recurrence occurred in one patient with macroscopically incomplete resection. Conclusions: ESD is an effective, safe, and feasible treatment for gastric GISTs. The frequency of complete resection is increased in EUS with an intraluminal growth pattern. [Table: see text]
A plasma-based analysis and genomic landscape of patients with high tumor mutational burden (TMB-H), microsatellite stable (MSS) colorectal cancer (CRC).
Authors: Anwaar Saeed, Reagan Barnett, Emil Lou, Luciana Madeira da Silva, May Thet Cho, Christopher Hanyoung Lieu, Marwan Fakih, Scott Kopetz, Jonathan M. Loree, Sepideh Gholami
Journal: Journal of Clinical Oncology (2023)

249 Background: An estimated 85% of CRC are microsatellite stable (MSS) and this population has limited response to immune checkpoint inhibitors (ICIs). Biomarkers are needed to identify responders. Although pembrolizumab received FDA universal approval for chemorefractory cancers with tissue TMB-H &gt; 10 mut/Mb, it is not effective across all TMB-H cancers. We aim to identify TMB-H/MSS CRC patients that derive benefit from ICIs through analysis of circulating tumor DNA (ctDNA). Methods: We retrospectively queried Guardant Health database (2020-2022) for patients with advanced CRC who had ctDNA NGS (Guardant360, Redwood City, CA) as part of routine clinical care. The assay covers a 1Mb panel for TMB that counts synonymous and non-synonymous somatic SNVs and indels to calculate a TMB score. Co-mutations were evaluated for MSS cancers with plasma TMB-H; ≥20mut/Mb vs those with low TMB (TMB-L; &lt; 20mut/Mb). RAS- mutated signature was defined as those harboring an activating somatic alteration in KRAS, NRAS, or BRAF. Statistical significance was calculated using Fisher’s exact test. Results: We identified 6412 CRC patients: 11% (711) TMB-H/MSS (median age 64), 69% (4426) TMB-L/MSS (median age 62), 3% MSI-H, and 17% unevaluable. When compared to TMB-L/MSS, patients with TMB-H/MSS had a significantly higher frequency of select genetic mutations, including TP53, APC, KRAS, EGFR, and PIK3CA (p &lt; 0.001). Treatment-naïve TMB-H/MSS cancers had a higher frequency of ARID1A (p = 0.05) and TERT (p = 0.02) alterations, while those post therapy progression had higher frequency of KRAS (p = 0.02), EGFR (p &lt; 0.001), and MAP2K1 (p = 0.002) alterations. A total of 556 (78%) CRC patients in the TMB-H/MSS cohort harbored a RAS-mutated genetic signature. Of those, 432 (78%) belonged to the post therapy progression group, likely representing adaptive clones post anti-EGFR therapy. While RAS-mutated tumors had a higher prevalence of PIK3CA (p = 0.001) and SMAD4 (p = 0.007) co-alterations, RAS-wildtype ones carried a higher frequency of ERBB2 (p = 0.068) alterations. Conclusions: We describe the genomic landscape of patients with plasma TMB-H/MSS CRC. A clinical cohort of TMB-H/MSS CRC patients identified by ctDNA and treated with ICIs will be presented.
Real-world outcomes in patients with gastroenteropancreatic neuroendocrine tumors receiving somatostatin analogue: Data from a public hospital in Brazil.
Authors: Kaique Ferreira Costa de Almeida, Fernanda Maris Peria, Matheus Guimaraes, Anny Alves Pereira, Liane Rapatoni
Journal: Journal of Clinical Oncology (2023)

650 Background: Neuroendocrine tumors are rare malignant neoplasms derived from endocrine cells and known for their heterogeneous behavior and histopathological characteristics; however, largely associated with a favorable clinical outcome. Somatostatin analogues (SSA) were initially used to control the symptoms of secretory neuroendocrine tumors, and later, they were considered effective as a first-line systemic treatment in unresectable or metastatic neuroendocrine tumors of the gastroenteropancreatic tract (NET-GEP). Randomized clinical trials are performed in controlled environments, with strict inclusion and exclusion criteria, and therefore, real-world studies can add to efficacy and safety data in the general population. Methods: To evaluate, in the real world scenario of a tertiary hospital of the public health system, the efficacy and toxicities of first-line treatment with somatostatin analogue in patients diagnosed with unresectable or metastatic NET-GEP, to find real-world progression free survival (rwPFS) and real-world overall survival (rwOS), in addition to the toxicity profile in our population and possible subgroups that benefit from first-line treatment, through the analysis of variables. Results: 29 patients met the study inclusion criteria, which were diagnosed in the period from 2009 to 2017. The median wrSLP and wrSG were 4.4 (95% CI 3.2 – 5.6) and 8.2 years (CI 95% 6.2 – 10.2), respectively. In an adjusted analysis of rwSLP, the HR for patients with hindgut tumors compared to midgut tumors was 4.41 with p 0.05, indicating that these patients had a 4x increased risk for disease progression (p 0 .05). In the adjusted analysis of wrSG, a trend towards a more favorable evolution was observed in the group of patients with well-differentiated tumors, with p 0.05. Assessment of toxicities revealed grade 2 and grade 3 adverse events in 34.48% of patients. Abdominal pain was the most incident toxicity, occurring in 17.24%, followed by headache (13.79%) and diarrhea (10.34%). Conclusions: Treatment with SSA was effective in our sample, with rwPFS and rwOS data above those found in randomized clinical trials. The toxicities were easily manageable and caused no documented harm to patients.
Body composition assessment in patients with gastric cancer.
Authors: Shun Nakamura, Kengo Kanetaka, Ryo Matsumoto, Yasumasa Hashimoto, Shinichiro Kobayashi, Junichi Arai, Kazuma Kobayashi, Shinichiro Ito, Masaaki Hidaka, Takeshi Nagayasu, Susumu Eguchi
Journal: Journal of Clinical Oncology (2023)

460 Background: The number of overweight patients with gastric cancer who underwent gastrectomy has increased in Japan. In addition to obesity, sarcopenia is a risk factor of severe surgical complication. The study aimed to elucidate the relationship between body composition and surgical outcome of gastrectomy for gastric cancer. Methods: This study was a retrospective, cohort study that include 701 patients who underwent gastrectomy in our institution between May 2008 and July 2017. Using preoperative computed tomography (CT), body composition such as psoas muscle index (PMI) and visceral fat area (VFA) were measured in the third lumber section. The patients were divided into two groups according to PMI (cut-off value 5.2 cm2/m2 in male and 3.5 in female) or VFA (cut-off value 155 cm2 in male and 116 in female), respectively. Surgical outcomes and postoperative complications were compared between the low and high groups for each PMI and VFA value. Results: There were 53 severe complications (14 anastomotic leakage, 14 pancreatic fistula, 8 respiratory failure, and 7b intraabdominal abscess) in this cohort. Some 701 patients were included in the study, 528 of whom were classified as normal PMI and 173 were as low PMI. In addition, 528 of whom were classified as normal VFA and 173 were as low PMI. In multivariate analysis, age and gender were independent risk factor for severe postoperative complication, however, low PMI was not. Conclusions: Our analysis showed no relationship between preoperative low PMI and postoperative complications. [Table: see text]
Comparison between interval and sporadic colon cancer in terms of clinicopathologic and molecular features.
Authors: Kyu Chan Huh, Dae Sung Kim, Jeong Eun Shin, Yoo Jin Lee, Kyeong Ok Kim, Jae Hyun Kim, Gyeong Hoon Kang
Journal: Journal of Clinical Oncology (2023)

205 Background: Interval colon cancer occurs due to either limitations of colonoscopy or rapidly developing new tumors, possibly reflecting molecular and environmental differences in tumorigenesis. This study aimed to compare the clinicopathologic and molecular features of interval colon cancer with those of sporadic colon cancer in Asia. Methods: This prospective, multicenter, cross‐sectional study was conducted from May 2017 to December 2021 at six university hospitals in South Korea. Interval colon cancer was defined as colon cancer diagnosed within 5 years of complete colonoscopy. We compared the clinicopathologic and molecular biological characteristics, including CpG island methylator phenotype (CIMP), KRAS, BRAF, and microsatellite instability (MSI), between patients with interval and sporadic colon cancers. Results: We compared and analyzed 28 patients with interval colon cancer and 72 patients with sporadic cancer. There was no difference in terms of sex, BMI, underlying disease, and family history in the clinical comparison between the interval and sporadic cancer groups. There was no difference in the location, shape, or stage of cancer including metastasis, between the two groups. In molecular biological analysis, CIMP was 5.1% positive for sporadic cancer and 17.9% positive for interval colon cancer, indicating an approximately 13% greater frequency in interval colon cancer (p = .036). KRAR mutation was observed in 36.7% of patients with sporadic cancers and 17.9% of those with interval colon, which was about 18% higher in sporadic cancer, but there was no statistically significant difference (p = .066). There was no difference between MSI and BRAF genotype between the sporadic and interval cancer groups. Conclusions: Unlike the findings of western studies, there was no clinical difference between sporadic and interval colon cancer. In molecular biological comparison, the CIMP positivity rate was significantly higher in patients with interval colon cancer.
Endoscopic submucosal dissection in early gastric cancer with papillary histological type.
Authors: Jung Hwan Lee
Journal: Journal of Clinical Oncology (2023)

412 Background: Gastric papillary adenocarcinoma has been regarded as differentiated-type adenocarcinomas along with well- or moderately-differentiated tubular adenocarcinomas in current endoscopic submucosal dissection (ESD) indication. We aimed to investigate lymph node metastasis (LNM) and to verify the safety of ESD in patients with papillary early gastric carcinoma (P-EGC). Methods: 4,264 patients with early gastric cancer (EGC) underwent curative gastrectomy between October 2000 and December 2017 at National Cancer Center, Korea. Among them, 45 patients were pathologically confirmed with P-EGC. We compared clinicopathological factors among differentiated-type EGC except P-EGC (n=2,106), undifferentiated-type EGC (n=2,113), and P-EGC. Logistic regression model was used to investigate risk factors of LNM. Results: P-EGCs were frequently located in lower third of the stomach (71.1%, P &lt; 0.001), and about half of them (46.7%, P &lt; 0.001) had elevated morphology. Mucosal cancer of P-EGC (37.9%) was significantly lower than differentiated-type (48.8%) and undifferentiated-type EGC (22.2%, P &lt; 0.001). Angiolymphatic invasion and LNM occurred most frequently in P-EGC (46.9% and 20.0%, respectively) compared to differentiated-type (18.9% and 9.2%, respectively) and undifferentiated-type EGCs (10.9% and 11.7%, respectively; P &lt; 0.001 and P = 0.004, respectively). P-EGC that was not mixed with other pathological type tended to have increased risk of LNM referent to differentiated EGC. (Odd ratio [OR] 2.53, 95% confidence interval [CI], 0.99-6.50). Among 45 patients with P-EGC, 13 patients met the current ESD indication; 3 patients corresponded to absolute indication and 10 patients did expanded indication. One patient had LNM and met expanded criteria with submucosal invasion less than 500 μm. In multivariate analysis, OR for LNM meeting expanded indication of P-EGC was 40.67 (95% CI, 2.54-702.76) referent to that of absolute indication compared to LNM meeting expanded indication of non-papillary EGC (10.28, 95% CI, 1.37-77.04). Conclusions: When ESD was applied to P-EGC, it should be carefully performed because of high rate of submucosal invasion and high risk of LNM even in with submucosal invasion less than 500 μm.